Effect Of RAS Blocking On The Expression Of NADPH Oxidase And INOS In Diabetic Rats Visceral Fat Tissue

Objective:Through high-fat feeding and low-dose streptozotocin intraperitoneal injection to establish diabetic rat model, to study the relation between glucose and lipid metabolism and oxidative stress and insulin resistance .To research the effect and related mechanism on glucose and lipid metabolism, insulin resistance of diabetic rats by blocking renin- angiotensin system (RAS).Methods :Fifty 8-week-old male Wistar rats were randomly divided into normal control group (10, general feeding) and the model group (40, high-fat and high-calorie feeding). The rats of model group were fed with high-fat and high-calorie diet eight weeks in order to inducing obesity–insulin resistance rat model .Diabetic rat model was induced by obesity–insulin resistance rat mode plus intraperitoneal injection of a small dose of streptozotocin. After 8 weeks intervention with Perindopril (AE group, n=10) or Valsartan (AR group, n=10),the concentration of malonaldehyde in plasma and fat tissue was detected and HOMA-IR was used to evaluate the degree of insulin resistance .At the same time, using histochemistry technical to observe the size of fat cells of each group and mRNA expression of iNOS and NADPH oxidase in perirenal adipose tissue were detected by RT-PCR method .Results:Compared with the NC group, weights of rats in DM group gradually decreased. While MDA levels in serum and fat tissue increased by 4.2 times and 2.46 times (both P<0.01), the expression of NADPH oxidase and iNOS mRNA in visceral fat tissue increased respectively 85% and 93.5% (P <0.05), and average area of fat cells increased 80% (P <0.05). After the intervention, compared with these of DM group, serum MDA levels in AE and AR groups declined respectively 35 % and 29% and fat tissue MDA levels dropped respectively 42% and 32% (all P <0.05).The expression of NADPH oxidase and iNOS mRNA in visceral fat tissue were declined by 26% and 29.6% (P <0.05)in AE Group, and respectively 28.5% and 31% (P <0.05) in AR Group. In AE and AR groups ,the sizes of fat cells reduced, while metabolism disorders of glucose and lipid and insulin resistance were improved.Conclusion:Oxidative stress station in visceral adipose tissue was enhanced significantly in diabetes state.Downregulating expression of NADPH oxidase and iNOS by blocking RAS singal transduction could attenuate oxidative stress station in visceral adipose tissue and improve glucose and lipid metabolism and insulin resistance.